Oxidative stress is a major cause of sporadic Parkinson's disease (PD). Here, we demonstrated that c-Abl plays an important role in oxidative stress-induced neuronal cell death. C-Abl, a nonreceptor tyrosine kinase, was activated in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced acute PD model. Conditional knockout of c-Abl in neurons or treatment of mice with STI571, a c-Abl family kinase inhibitor, reduced the loss of dopaminergic neurons and ameliorated the locomotive defects induced by short-term MPTP treatment. By combining the SILAC (stable isotope labeling with amino acids in cell culture) technique with other biochemical methods, we identified p38α as a major substrate of c-Abl both in vitro and in vivo and c-Ablmediated phosphorylation is critical for the dimerization of p38α. Furthermore, p38α inhibition mitigated the MPTP-induced loss of dopaminergic neurons. Taken together, these data suggested that c-Abl-p38α signaling may represent a therapeutic target for PD. Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by bradykinesia, rigidity, tremor, and loss of dopaminergic neurons. 1 Familial mutations that cause PD have been identified, including in the genes that encode α-synuclein and leucine-rich repeat kinase 2 (LRRK2) that cause autosomal-dominant PD, and DJ-1, PINK1, and parkin that cause autosomal-recessive PD. 2 However, the majority of PD cases are sporadic. The cause of sporadic PD remains unknown, and the role of environmental toxins and genetic factors in sporadic PD is unclear. However, the evidence regarding postencephalitic PD and the discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced Parkinsonism suggest that environmental toxins may be a major cause of sporadic PD. 3,4 The neurotoxins used to induce dopaminergic neurodegeneration, including 6-hydroxydopamine, MPTP, and rotenone, induce the formation of reactive oxygen species (ROS). ROS react with nucleic acids, proteins, and lipids to induce mitochondrial damage. Although oxidative stress plays a critical role in causing PD, the mechanisms underlying oxidative stress-induced PD remain unclear.The nonreceptor tyrosine kinase c-Abl is ubiquitously expressed and mediates a variety of extrinsic and intrinsic cell signaling activities, including growth factor signaling, cell adhesion, oxidative stress, and DNA damage. 5 Our group and other groups have reported that c-Abl plays an important role in oxidative stress-induced neuronal death. 6-8 Recently, Ko et al. 9 and Imam et al. 10 have reported that c-Abl phosphorylated Parkin and inhibited its E3 ligase activity that led to the neurotoxic accumulation of Parkin's substrates. α-Synuclein has also been reported to be substrates of c-Abl and to participate in PD pathogenesis. 9-11 The c-Abl inhibitor Nilotinib and INNO-406 have been reported prevents the loss of dopamine neurons and improves motor behavior in a murine PD model. [12][13][14] In this study, we demonstrated that c-Abl ...

Plants that hyperaccumulate metals are ideal subjects for studying the mechanisms of metal and mineral nutrient uptake in the plant kingdom. Indian Mustard (Brassica juncea) has been shown to accumulate moderate levels of Cd, Pb, Cr, Ni, Zn, and Cu. In this experiment, 10 levels of Cd concentration treatments were imposed by adding 10-190 mg Cd kg(-1) to the soils as cadmium nitrate [Cd(NO3)2]. The effect of Cd on phosphorus (P), potassium (K), calcium (Ca), magnesium (Mg), and the micronutrients iron (Fe), manganese (Mn), copper (Cu), and zinc (Zn) in B. juncea was studied. Plant growth was affected negatively by Cd, root biomass decreased significantly at 170 mg Cd kg(-1) dry weight soils treatment. Cadmium accumulation both in shoots and roots increased with increasing soil Cd treatments. The highest concentration of Cd was up to 300 mg kg(-1) d.w. in the roots and 160 mg kg(-1) d.w. in the shoots. The nutrients mainly affected by Cd were P, K, Ca, Fe, and Zn in the roots, and P, K, Ca, and Cu in the shoots. K and P concentrations in roots increased significantly when Cd was added at 170 mg kg(-1), and this was almost the same level at which root growth was inhibited. Zn concentrations in roots decreased significantly when added Cd concentration was increased from 50 to 110 mg kg(-1), then remained constant with Cd treatments from 110 to 190 mg kg(-1). However, Zn concentrations in the shoots seemed less affected by Cd. It is possible that Zn uptake was affected by the Cd but not the translocation of Zn within the plant. Ca and Mg accumulation in roots and shoots showed similar trends. This result indicates that Ca and Mg uptake is a non-specific process.

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